Trends of frequency, mortality and risk factors among patients admitted with stroke from 2017 to 2019 to the medical ward at Kilimanjaro Christian Medical Centre hospital: a retrospective observational study

Objective The burden of stroke has increased in recent years worldwide, particularly in low-income and middle-income countries. In this study we aim to determine the number of stroke admissions, and associated comorbidities, at a referral hospital in Northern Tanzania. Design This was a retrospective observational study. Setting The study was conducted at a tertiary referral hospital, Kilimanjaro Christian Medical Centre (KCMC), in the orthern zone of Tanzania. Participants The study included adults aged 18 years and above, who were admitted to the medical wards from 2017 to 2019. Outcome The primary outcome was the proportion of patients who had a stroke admitted in the medical ward at KCMC and the secondary outcome was clinical outcome such as mortality. Methods We conducted a retrospective audit of medical records from 2017 to 2019 for adult patients admitted to the medical ward at KCMC. Data extracted included demographic characteristics, previous history of stroke and outcome of the admission. Factors associated with stroke were investigated using logistic regression. Results Among 7976 patients admitted between 2017 and 2019, 972 (12.2%) were patients who had a stroke. Trends show an increase in patients admitted with stroke over the 3 years with 222, 292 and 458 in 2017, 2018 and 2019, respectively. Of the patients who had a stroke, 568 (58.4%) had hypertension while 167 (17.2%) had diabetes mellitus. The proportion of admitted stroke patients aged 18–45 years, increased from 2017 (n=28, 3.4%) to 2019 (n=40, 4.3%). The in-hospital mortality related to stroke was 229 (23.6%) among 972 patients who had a stroke and female patients had 50% higher odds of death as compared with male patients (OR:1.5; CI 1.30 to 1.80). Conclusion The burden of stroke on individuals and health services is increasing over time, which reflects a lack of awareness on the cause of stroke and effective preventive measures. Prioritising interventions directed towards the reduction of non-communicable diseases and associated complications, such as stroke, is urgently needed.

INTRODUCTION: 1.) The last sentences of the 3rd and 4th paragraphs is identical. 2.) The authors seem to undermine the purpose of their study in the introduction by stating definitively that stroke admissions are increasing over time and that females are beginning to make up the preponderance of stroke admissions in sub-Saharan Africa, making their stated purpose -to determine if stroke admissions are increasing -and one of their findings -that females make up the majority of the population -less compelling. Furthermore, it seems that some of this work and these findings have already come from their institution. Please clarify in this section why the presented work is still important and unique. SPECIFIC OBJECTIVES 1.) It seems objectives 1 and 3 are very similar and could be combined. Also, generally these are included in the last paragraph of the introduction rather than a separate manuscript section. METHODS 1.) This section can be rewritten in paragraph form with fewer subsection as is typical for a manuscript. 2.) Please justify why patients admitted to the ICU were excluded as it seems this may have biased the study to omit the most severe strokes.

RESULTS
1.) I am unclear why pneumonia and UTI are included in comorbidities along with other comorbidities that are stroke risk factors. It seems these are likely post-stroke/in-hospital complications rather than associated with stroke occurrence. 2.) Page 15/  Table 3 and the text states that the majority of stroke patients (n=458) had a length of stay >30 days, but the percentage listed is 12.8%. Furthermore, there are ~7000 nonstroke patients, and the table states 3117 had a length of stay >30 days. This should be less than half of the non-stroke patients, but the percentage listed is 87.2%. Please clarify. 4.) The abstract states that between 2% and 6% of annual admissions were due to stroke, but the results state that the overall prevalence of stroke was 12.2% (last sentence on page 13). Please clarify how this is possible. 5.) It is somewhat misleading to state that the "proportion of overall stroke admissions" was 22, 30 and 47% over the three years. The wording suggests you are comparing the proportion of all admissions that were stroke admissions, which seems the most straightforward way to present these data since this manuscript is looking at whether the burden of stroke admissions in the medicine department is increasing. Rather, you are reporting the proportion of all stroke admissions that occurred in each year. This proportion could be very misleading. For example, what if the total number of admissions to the medicine wards doubled in one year? If that was the case, you could see a huge increase in the proportion of total stroke admissions that occurred that year without actually seeing an increasing proportion of the admissions ot the medicine wards due to stroke.

DISCUSSION:
1.) I am still unclear why the association with pneumonia is being interpreted as a potential causal mechanism for stroke as it seems it is in the last sentence of the 1st paragraph. Isn't it more likely that pneumonia occurs after the stroke due to aspiration? 2.) In general, new results should not be initially presented in the Discussion. From my reading of the results, there is no report that older patients were more likely to have multiple comorbidities. Please present this data in the results section. 3.) Again, in the discussion, in-hospital mortality rate is reported as 23.5% but is reported as 15% in the results. Please clarify. 4.) The discussion states hypertension was present in 24% of participants but the results state it was present in 58%. Please clarify. 5.) In the Discussion, it is important to try to put the results of other studies that you report in the context of your results. In many parts of this discussion, it reads as literature review. It would significantly strengthen the discussion if you report the results of another study to then put those results in the context of your own findings. WEre they similar to or different than this study's findings? If different, why might these differences be? It is also important to give context to reported results. For example, lines 18 and 19 on page 17 quote a study with a diabetes prevalence of 10% but the location of this study is not mentioned and is crucial to putting these results in contect. 6.) It is important to add a discussion of the strengths and limitations of the paper. 7.) A conclusion paragraph is usually added at the end of the Discussion. 8.) It is not standard manuscript format to include an "extras" section. This is an interesting fact that should be incorporated and contextualized within the rest of the Discussion section.
MINOR: 1.) The "key messages" section could use editing for grammatical clarity.

Reviewer comments Action Page number and line number
Please remove the 'Key message' section.
We thank the reviewer for bringing this to our attention, hence removed.

Page 4
Please ensure that you have fully discussed the methodological limitations of the study in the Discussion section of the main text.
We have added methodological limitations in discussion section.
What is the health care system, the organization of the hospital in a country like Tanzania?
We have added an explanation of the healthcare system and organization in Tanzania.
Study setting section, Page 6, first nine lines.
What is medical ward? We thank the reviewer for bringing this, Medical ward is a hospital unit or department where patients are admitted and treated for medical conditions that require non-surgical care.
We have added a respective definition to the manuscript.
Who is treated in the medical ward and who in other departments of the hospital?
Patients who are treated or admitted to the medical ward include those with chronic illnesses such as diabetes, hypertension, heart disease, lung disease, kidney disease, and liver disease. They may also include patients with infectious diseases. A sentence explaining which patients are treated in the medical ward has been added to the study setting section.
The hospital has an in-patient capacity of 634 beds of which 100 are in the medical ward (Explanation).
The entirety of the hospital is capable of admitting 634 patients at full capacity within which 100 belong to the internal medicine department also referred to as medical wards. The explanation has been added to the paper.
Study setting section page 7, first three lines.
What is internal medicine? Thank you, reviewer, for rising this, the description of the term is given as requested.
The reason for excluding all patient under Intensive care unit.
We excluded patients who were admitted straight to ICU and who either died there or were discharged from there but have included those who were admitted to a medical ward and subsequently transferred to ICU. Very few individuals will have been directly admitted to ICU and missing information of the variables of interest.
Eligibility criteria section, Page 9, first two lines.
A description of the structure of the hospital.
KCMC is organized into departments incl. internal medicine, general surgery, Study setting section, Page 6, last five lines, and first five lines in Page 7.
orthopedic, pediatrics, obstetrics and gynecology and cancer unit.
It is also necessary to expand all abbreviations in the text and in the table descriptions.
List of abbreviations expanded. Page 2.

Problem statement and justification
We have added an explanation of the problem and the rationale.
Page 5, Introduction section, line 8-11 The last sentences of the 3rd and 4th paragraphs are identical.
We thank the reviewer for bringing this to our attention and have removed one of the sentences.
Please clarify in this section why the presented work is still important and unique.
We thank the reviewer for bringing this. In Tanzania the previous stroke incidence is known but still efforts are needed by policymakers to monitor the incidence and primary prevention is needed to reduce the number of stroke admissions as there are very limited recent data.
Page 5, Introduction section, line 8-12 It seems objectives 1 and 3 are very similar and could be combined The objectives have been updated.
Page 5, Objective section, last five lines Objective one and three are included in the last paragraph of the introduction rather than a separate manuscript section.
We agree with the reviewer and now the objectives have been removed and added to the objective section where they should be.
Introduction section, Page 5 The methods section can be rewritten in paragraph form with fewer subsection as is typical for a manuscript.
Changes made as requested. Method section, page 6-9.
Please justify why patients admitted to the ICU were excluded as it seems this may have biased the study to omit the most severe strokes.
We included patients who were admitted to a medical ward first and then transferred to ICU, and excluded patients who were admitted straight to ICU and either died there, or were discharged from there. Very few individuals will have been directly admitted to ICU and missing information of the variables of interest.
Page 10, exclusion criteria section first three lines.
Why pneumonia and UTI are included in comorbidities along with other comorbidities that are stroke risk factors. It seems these are likely post-stroke/inhospital complications rather than associated with stroke occurrence.
We agree that pneumonia and UTI are complications of stroke rather than risk factors. Hence these have been edited.
The abstract states that in-hospital mortality was 23.6% while this section states it is 15.9%. Please clarify.
23.6% is the overall mortality for all hospital admissions while 15.9% is mortality for only stroke patients. This has been clarified.
Please double check these numbers as they do not make sense. Table 3 and the text states that the majority of stroke patients (n=458) had a length of stay >30 days, but the percentage listed is 12.8%. Furthermore, there are ~7000 non-stroke patients, and the table states 3117 had a length of stay >30 days. This should be less than half of the non-stroke patients, but the percentage listed is 87.2%. Please clarify.
We agree with the reviewer and have hence corrected the percentage in table 3 accordingly.
At first, it was the column percentage.
Page 13, result section ( Table-3) The abstract states that between 2% and 6% of annual admissions were due to stroke, but the results state that the overall prevalence of stroke was 12.2% 2.8%, 3.6% and 5.7% are stroke prevalence for the year 2017, 2018 and 2019 respectively. And 12.2% is overall prevalence for the entire three years.
It is somewhat misleading to state that the "proportion of overall stroke admissions" was 22, 30 and 47% over the three years. The wording suggests you are comparing the proportion of all admissions that were stroke admissions, which seems the most straightforward way to present these data since this manuscript is looking at whether the burden of stroke admissions in the medicine department is increasing. Rather, you are reporting the proportion of all stroke admissions that occurred in each year. This proportion could be very misleading. For example, what if the total number of admissions to the medicine wards doubled in one year? If that was the case, you could see a huge increase in the proportion of total stroke admissions that occurred that year without actually seeing an increasing We agree with the reviewer the percentage was calculated considering the stroke as denominator, but in this case taking the overall admission as the denominator will make sense. So, in that case the proportions will read as 9.4%,11.9%,14.5%.
Discussion section, Page 16, last seven lines.
Also see figure 4.
proportion of the admissions to the medicine wards due to stroke.
Explanation on the discussion section on why the association with pneumonia is being interpreted as a potential causal mechanism for stroke as it seems it is in the last sentence of the 1st paragraph. Isn't it more likely that pneumonia occurs after the stroke due to aspiration?
We agree that pneumonia and UTI are complications of stroke rather than risk factors. Hence these have been edited.
In general, new results should not be initially presented in the Discussion. From my reading of the results, there is no report that older patients were more likely to have multiple comorbidities. Please present this data in the results section.
We agree with the reviewer that the results need to be initially presented in the results section and have made the relevant changes.
In the discussion, in-hospital mortality rate is reported as 23.6% but is reported as 15% in the results. Please clarify. In the Discussion, it is important to try to put the results of other studies that you report in the context of your results.
(Restructure the discussion section) The discussion has been restructured, by involving what others has done in this area.
Page 17, discussion section, last 8 lines It is important to add a discussion of the strengths and limitations of the paper.
We agree with the reviewer and have hence added a strength and limitations description in the discussion section.
A conclusion paragraph is usually added at the end of the Discussion.
It is not standard manuscript format to include an "extras" section. This is an interesting fact that should be incorporated and contextualized within the rest of the Discussion section.
We agree with the reviewer and the conclusion paragraph has been included at the end of the discussion section.
Page 18, sectiondiscussion, line 10-13 In addition to the reviewers' directly requested changes, we

GENERAL COMMENTS
The authors have satisfactorily responded to my initial concerns about the manuscript. The statistics, in particular, are much improved and, I believe, presented in a more meaningful and interpretable way. I believe this manuscript is an important addition to the literature.

VERSION 2 -AUTHOR RESPONSE
have added some additional clarifications and language changes to improve the overall comprehensibility and language of the manuscript. We have highlighted these changes in the "changes highlighted" document.